Download QA282_3_orlistatandlevothyroxinefinal

Medicines Q&As
Q&A 282.3
Is there an interaction between orlistat and levothyroxine?
Prepared by UK Medicines Information (UKMi) pharmacists for NHS healthcare professionals
Before using this Q&A, read the disclaimer at www.ukmi.nhs.uk/activities/medicinesQAs/default.asp
Date prepared: 2nd January 2014
Background
Orlistat is an anti-obesity drug available on prescription as a 120mg capsule (Xenical®), or over-thecounter as a 60mg capsule (Alli®). The National Institute for Health and Clinical Excellence (NICE)
recommends that orlistat is used in adults with a body mass index (BMI) of 30 or with a BMI of 28 or
more along with associated risk factors and is initiated after dietary and lifestyle changes have been
attempted but a target weight has not been reached by these measures alone (1). The Medicines and
Healthcare Regulatory Agency (MHRA) issued a Drug Safety Update in February 2010 which raised
awareness of a possible interaction between levothyroxine and orlistat (2). This Q&A details the
current evidence behind this interaction and how to manage patients.
Answer
Orlistat acts by inhibiting lipases in the stomach and small intestine, which in turn means that
triglycerides in dietary fat are not broken down into fatty acids. This reduces absorption of fat into the
body. Undigested fat is then excreted in the faeces. Orlistat is minimally absorbed systemically and
appears to be mainly metabolised in the gastro-intestinal tract. The majority of the drug is excreted
unchanged in the faeces (3). Side effects of orlistat are mainly mild to moderate gastro-intestinal
effects but rarely serious liver disorders have been reported (2).
Evidence of Interaction
Only two case reports of an interaction between levothyroxine and orlistat have been reported in the
literature. One details a 46 year old woman who was taking 250 micrograms of levothyroxine following
total thyroidectomy due to papillary carcinoma of the thyroid. Two weeks after commencing orlistat
therapy, she suffered symptoms of hypothyroidism which improved following withdrawal of orlistat and
an increase of levothyroxine to 300 micrograms (4). The other case report describes a 43 year old
woman who experienced a gradual change is TSH levels, requiring an increase in dosage of
levothyroxine. Following discontinuation of orlistat, her TSH levels normalised with a resulting slow
decrease in dosage (5).
Mechanism of interaction
Due to its rarity, the cause of this interaction is as yet unknown, but it is postulated that orlistat may
bind to levothyroxine, limiting its absorption into the gastro-intestinal tract (3). To date, no common
metabolism pathways or plasma protein binding sites have been discovered for the two drugs (5).
Levothyroxine absorption is decreased by steatorrhoea and malabsorption, which may occur due to
the action of orlistat (6). Another mechanism may be a reduced absorption of iodine salts. Iodine salts
are converted to iodide in the gastro-intestinal tract, which in turn is oxidised and incorporated into
levothyroxine (T4) and tri-iodothyronine (T3) (7). Hence reduction in iodine absorption may lead to
hypothyroidism.
Management of Interaction
The summary of product characteristics (SPC) for Alli® was amended in 2009 to include a warning
regarding hypothyroidism and to clarify that patients wishing to take orlistat should speak to their GP
prior to treatment (8). As evidence of the clinical importance of this interaction is lacking however, the
possibility of an interaction should not stop co-administration of these drugs. The administration of
levothyroxine and orlistat should be separated by 4 hours, and increased monitoring of the patient’s
thyroid hormone levels may be prudent (9, 10).
Available through NICE Evidence Search at www.evidence.nhs.uk
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Medicines Q&As
Summary
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A potential interaction exists between levothyroxine and orlistat.
This may be due to reduced absorption of levothyroxine, or iodine, or both.
This interaction is not a contra-indication to use of orlistat along with levothyroxine.
Patients should be advised to speak to their GP prior to purchasing orlistat over-the-counter if
they are also taking levothyroxine.
Orlistat and levothyroxine should be administered at least 4 hours apart.
The patient’s thyroid hormone levels should be monitored.
Limitations
Documented evidence of this interaction is lacking, so the available evidence is difficult to interpret.
Quality Assurance
Prepared by
Hayley Johnson, Regional Drug & Therapeutics Centre, Newcastle upon Tyne
Date Prepared
2nd January 2014
Checked by
Vincent Cassidy, Regional Drug & Therapeutics Centre, Newcastle upon Tyne
Date of check
3rd January 2014
Search strategy
Embase: *Tetrahydrolipstatin OR Orlistat.af AND *levothyroxine OR *thyroxine AND *hypothyroidism
AND *hyperthyroidism
Medline: Orlistat.af AND *thyroxine
Orlistat.af AND (*hypothyroidism OR) *hyperthyroidism
NICE website
MHRA website
Electronic Medicines Compendium
Micromedex
Medicines Complete
References
1. CG43 Obesity: Full Guideline, Section 1 - Introduction, Methods and Recommendations. National
Institute of Health and Clinical Excellence, 2010; 119-124
2. MHRA Drug Safety Update, 2010; (3)7; 4-5
3. Summary of Product Characteristics- Xenical (orlistat). Roche Products Limited. Accessed via
http://www.medicines.org.uk/emc/medicine/1746/SPC/Xenical+120mg+hard+capsules/ on
02/01/2014. Last updated on the eMC: 11/09/2013
4. Madhava K and Hartley A. Hypothyroidism in Thyroid Carcinoma Follow-up: Orlistat May Inhibit
the Absoprtion of Thyroxine. Clinical Oncology; 2005 (17) 492-493
5. Chiffoleau A, De Mallmann V, Lambet J et al. Interaction between orlistat and levothyroxine : a
first French case report. Fundamental and Clinical Pharmacology; 2010: 24(1) 0767-3981
6. DRUGDEX®System Levothyroxine DrugDex Evaluation in: Klasco RK (Ed): DRUGDEX® System
(electronic version). Truven Health Analytics Micromedex, Greenwood Village, Colorado, USA.
Available at: https://www.micromedexsolutions.com (cited: 02/01/2014).
7. Sweetman S (Ed) Martindale: The Complete Drug Reference. [online] London: Pharmaceutical
Press. Accessed via http://www.medicinescomplete.com/mc/martindale/current/9000-a5-z.htm on
02/01/2014
Available through NICE Evidence Search at www.evidence.nhs.uk
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Medicines Q&As
8. Glaxo SmithKline Letter to Health Professionals. Accessed via
http://www.mhra.gov.uk/home/groups/pl-p/documents/websiteresources/con068267.pdf on
02/01/2014
9. DRUGDEX®System Orlistat DrugDex Evaluation in: Klasco RK (Ed): DRUGDEX® System
(electronic version). Truven Health Analytics Micromedex, Greenwood Village, Colorado, USA.
Available at: https://www.micromedexsolutions.com (cited: 02/01/2014).
10. Baxter K (ed), Stockley’s Drug Interactions. [online] London: Pharmaceutical Press. Accessed via
http://www.medicinescomplete.com/mc/martindale/current/9000-a5-z.htm on 02/01/2014
Available through NICE Evidence Search at www.evidence.nhs.uk
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